Effects of Ca²⁺ on rabbit translens short-circuit current: Evidence for a Ca²⁺ inhibitable K⁺ conductance

Purpose. To characterize the effects of medium Ca²⁺ levels on rabbit lens electrical properties. Early studies with wholly submerged lenses had shown that Ca²⁺ removal from the bath resulted in an increased Rb⁺ efflux, a consequence of an increased Na⁺ permeability and lens depolarization. Methods. Lenses were bathed within Ussing-type chambers under short-circuited conditions, an arrangement in which the translens short-circuit current (I(sc)) is carried across the posterior lens surface mainly by an influx of Na⁺, and across the anterior face largely by a K⁺ efflux. Results. Under the present conditions in which the effects of Ca²⁺ were characterized unilaterally, the above established effects could only be ascribed to the posterior surface. When Ca²⁺ removal was limited to the anterior face, the I(sc) increased from 11.87 ± 1.17 to 17.04 ± 1.52 μA/cm² (means ± SE's, n = 18; an accompanying translens resistance (R(t)) decrease of 0.23 ± 0.049 KΩ cm² was also recorded). Conversely, increasing the control, anterior-bath [Ca²⁺] from 1.8 to 3.6 mM reduced the K⁺ efflux-dependent I(sc) from 10.54 ± 1.09 to 8.93 ± 1.02 (n = 10, with an R(t) increase of 0.11 ± 0.013). These changes were reversible, Na⁺-independent, and fully inhibited by the presence of K⁺ channel blockers (quinidine or Ba²⁺). Inhibitions of the Ca²⁺ effects were also obtained with strontium, a Ca²⁺ surrogate. The I(sc) was less responsive to changes in the Ca²⁺ content of the posterior bath. Removal of the cation caused a grad ual 1.65 ± 0.72 μA/cm² increase (n = 9, with an R(t) decrease of 0.090 ± 0.021 KΩ cm²). In the absence of posterior Na(±), Ca²⁺ withdrawal resulted in highly variable responses, with some specimens exhibiting salient current increases, suggesting that an outwardly directed, posterior efflux of an anion could also have been affected. During the course of this study it was consistently observed that the removal of Na(±) from the anterior bath led to an I(sc) decrease of 2.62 ± 0.22 μA/cm² (n = 32, with an R(t) increase of 0.35 ± 0.029 KΩ.cm²). This change occurred in both the presence of ouabain and the absence of Ca²⁺, suggesting that it did not result from an inhibition of the Na⁺-K⁺ pump current nor from a reversal in putative Na⁺/Ca²⁺ exchange activity. Small I(sc) increases upon anterior Na⁺ withdrawal (1.68 ± 0.17, n = 7), consistent with Na⁺ efflux from the lens, could only be observed with K⁺ channels inhibited with Ba²⁺. Also congruent with the observations of a relatively limited anterior Na⁺ permeability, was the finding that the induction of nonspecific cation channels with amphotericin B reduced the I(sc) by allowing Na⁺ from the anterior bath to enter the lens. Thus, changes in lens I(sc) can differentiate changes in K⁺ permeability across the native anterior epithelium from changes in Na⁺ permeability. Conclusions, Overall, these results suggest that lens Ca²⁺-mobilizing agents (e.g. acetylcholine) could trigger the inhibition of epithelial K⁺ conductance(s) by the direct action of Ca²⁺on K⁺ channels.